Phenol → 4,5,6,7-Tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-pyrazolo[1,5-a]pyrazine

HRID 1773771Notes

Reaction equation

N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:36]1([OH:42])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[C:43]1([CH2:49][N:50]2[CH2:55][CH2:54][N:53]3[N:56]=[C:57]([CH2:59]O)[CH:58]=[C:52]3[CH2:51]2)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C1COCC1>[O:42]([CH2:59][C:57]1[CH:58]=[C:52]2[CH2:51][N:50]([CH2:49][C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH2:55][CH2:54][N:53]2[N:56]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Di-tert-butyl azodicarboxylate (0.76 g, 3.3 mmol) was added to a stirred solution of triphenylphosphine (0.87 g, 3.3 mmol), phenol (0.31 g, 3.3 mmol) and 4,5,6,7-tetrahydro-5-(phenylmethyl)-pyrazolo[1,5-a]pyrazine-2-methanol (1.2 mL, 2.75 mmol) in THF (0.6 mL) in a sealed tube and under N2. The mixture was stirred at 120° C. for 20 minutes under microwave irradiation and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected and the solvents were evaporated in vacuo to yield 4,5,6,7-tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-pyrazolo[1,5-a]pyrazine (0.65 g, 74% yield) as a colorless oil that precipitated upon standing. C20H21N3O LCMS: Rt 3.03, m/z 320 [M+H]+ (see LCMS Method 1).

Workup

customthe solvents were evaporated in vacuo
customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
customThe desired fractions were collected
customthe solvents were evaporated in vacuo

Sources & evidence

ORD record: ord-881679bb3a0a47a894d02353e339f0ce
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09255103B2

Reaction notes

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